The overall objectives of the research program entitled "Proteins in Multiple Myeloma and Related Blood Diseases" will be to acquire further knowledge of antibody structure and diversity through correlative immunochemical, biochemical, physicochemical, genetic, and functional properties of the homogeneous immunoglobulins (Bence Jones proteins, myeloma proteins, and Waldenstrom macroglobulins) found in patients with multiple myeloma and related B cell malignancies. Studies of the monoclonal immunoglobulin components in these and other patients with neoplastic and inflammatory diseases are proposed to provide further information on the diagnostic, therapeutic, and prognostic importance and the functional significance of such proteins as biomarkers of cancer and of the humoral immune system. The specific aims will be directed toward the establishment of concordance between immunochemical and structural features of human immunoglobulins, with emphasis on utilizing immunochemical techniques to provide a rapid and sensitive means for detecting and localizing structural differences in the amino-terminal or variant half (VL) and in the carboxyl-terminal or constant (CL) half of the light polypeptide chains of immunoglobulins; the characterization of physical, chemical, immunochemical, genetic, and other biologic properties of the V and C domains of light chains; the study of the formation and functional significance of the homogeneous units, subunits, and fragments of immunoglobulins found in the serum or urine of patients with B cell-related malignancies and of patients with other types of cancer of inflammatory diseases; and to ascertain further the therapeutic and prognostic usefulness of monoclonal immunoglobulins as biomarkers of cancer, especially to determine the frequency and significance of chemotherapeutically-associated immunoglobulin alterations as presaging the development of a second malignancy in a patient with cancer.